Virtual Reality Modelling Language (VRML) in Chemistry

aPresent address: Molecular Simulations Ltd,
240/250 The Quorum, Barnwell Road, Cambridge CB5 8RE England
bDepartment of Chemistry, Imperial College,
London, SW7 2AY.
The number of chemistry-related World-Wide Web sites has grown
from a few hundred since our introductory review in 19951 to around 3600 by early 1998.2 Much of the chemical content of these
sites has been expressed using Hypertext-markup language
(HTML), incorporating hyperlinks in the form of the now
familiar URL (Uniform Resource Locator) to create associations
with other documents and sites, and to reference visual content
such as two-dimensional images, diagrams and schemes. Since
1994 however, a number of novel technologies have been
introduced to the Web which go beyond the use of simple images.
Here we will focus on one such method termed Virtual Reality
Modelling Language or VRML, which has been applied in a number
of chemically interesting ways.

The limitations of Images

The basic object collection used to construct a document in
HTML is the ASCII character set which includes the letters you
are reading now, together with some specially reserved control
characters such as < or >. Together with some Greek
symbols (which are actually not handled well in HTML), highly
complex chemical meanings, semantics and data can be expressed.
Chemistry however can be a particularly visual subject, and
many of our models and data of molecular behaviour and
structure are most easily comprehended and disseminated using
visual means of expression. On the Web, most visual
illustrations have hitherto been derived from bit-mapped
digital formats, or images as they are known. As devices for
expressing chemical content and meaning, such images offer
little advantage over the use of print, and suffer from the
same limitations such as the great difficulty in indexing of
and searching for the meaning they carry. Another limitation
(or advantage, depending on your point of view) is that such
illustrations show only their author's interpretation and
selected viewpoint of a particular chemical concept or
expression of data and are subject to copyright control. The
reader cannot select any other viewpoint or impose upon that
viewpoint any other style, nor can they easily recover in an
error-free manner any of the original data or information used
to generate the illustration, or indeed copy the image without
permission.

The Importance of Models

We believe that a superior approach lies in defining
multi-dimensional models wherever practicable, rather than in
creating static 2D illustrations. Such models could if needed
have attributes of time-dependence (i.e. animation),
sounds and behaviour controlled by specified algorithms.
Virtual reality modelling language (VRML) was born at a
workshop at the first World-Wide Web conference held in Geneva
in May 1994 as an expression of this need, and even then
chemical applications were envisaged.3 The first definitions of this new
framework emerged in October 1994 and became standardised as
version 1 during 1995. This was superceded by VRML 2 in 1996,
and has now been renamed VRML 97.4
It is worth emphasizing that VRML was designed as a generic
modelling language, in contrast to HTML, which is a markup
language. Markup is a mechanism which allows the author to
express semantics and can thus be used to provide fine grained
structure and relationships in a document. Such internal
structure in turn allows indexing of the content. VRML, as a
modelling language, is currently less suited for semantic
expression, and hence for operations such as indexing.

To illustrate the difference between a modelling and a
markup language, consider how an atom might be described. HTML
itself has no well defined mechanism for defining an atom, and
one has to use a markup language such as CML5 (Chemical Markup Language, which is an
implementation of XML, itself an evolutionary successor to
HTML) to define an atom and properties such as atomic number,
its connectivity to other atoms, the number of electrons
associated with it and so forth. Using VRML, one would define
the same atom as an spherical object, with model properties
such as colour, radius, 3D co-ordinates, lighting and motion
attributes, and if necessary associate this object with
scriptable actions such as collision avoidance with other
objects (computed if necessary using e.g. molecular mechanics
force fields). VRML is therefore complementary to a markup
language since it defines a quite different set of primitive
and importantly three-dimensional objects which can be used to
express complex chemical models in a visual manner. Copyright
implications for models are also different from illustrations,
in part because models are specified using data provided by
their author, and only created in a specific viewable style by
the actions of the reader and the software they are using.

The Characteristics of a VRML Model

The first thing one notices about a VRML model is that it must
be navigated using a quite different set of metaphors from that
used for a page of HTML-derived text. The dashboard controls
(Model 1), which are probably more familiar to a rather younger
generation of fast-action games console owners than to most
chemists, contain some fascinating differences from printed
documents and HTML-browser pages. Whereas a search-index or the
"find" browser button for example can be used to easily locate
occurances of a specific set of objects (characters) within a
printed or HTML based document, no such option is currently
possible in a VRML model. The best one can do in this regard is
to "seek" an already visible object by changing the viewpoint
of the model to approach it more closely. Another option found
on a page of displayed text and images is the print button; an
option conspicuously missing from VRML controls. This would
imply that any electronic publication which might make
extensive use of models to convey chemical information could
not have any directly equivalent printed form. This very
article is one such example; what you are viewing here of
course are illustrations reduced from the information provided
by models.

One page-derived metaphor does carry over; the author of a
model can insert the equivalent of section headings (called
viewpoints) to emphasise what they believe are important
characteristics of their model, and in the process also provide
the equivalent of keywords ("meta-data") to assist in any
indexing of their model. A rather less desirable characteristic
of VRML models is that even minor syntactic errors in their
specification (the equivalent of spelling mistakes or errors in
the markup of an HTML document) will probably render the entire
model unviewable, a contrast with component-based HTML
documents which fail more gracefully in failing to properly
display only the component with the error. This intolerance of
errors is probably one reason why the application of VRML is
still relatively low.

Model 1.Navigation Dashboard for a VRML Model,
deriving from the CosmoWorld viewer.

Viewing and Creating VRML Models

The widespread adoption of VRML has also been limited by the
need to use relatively powerful computers. Only in the last
year has the introduction of low cost, fast (>200MHz)
computers equipped with powerful graphical capabilities born
from the need to sell computer games, and adequate memory (>
32 Mbyte), coupled with the release of software such as
CosmoPlayer6 made viewing VRML models a practical
reality for the average computer owner. CosmoPlayer can view
VRML 2.0/97 models and comes in the form of a plug-in for use
with Web clients such as Netscape.

Creating VRML worlds is more complex than authoring an HTML
document, and invariably requires the acquisition of suitable
software. A good generic package is CosmoWorlds6, whilst for chemical applications,
programs such as WebLab Viewer Pro7
or EyeChem8 are available. Several
"filters" for converting standard chemical coordinate formats
such as PDB also exist.9

The Application of VRML Models in Chemistry

1. Complex Molecular models

VRML has been applied to many
areas of chemistry9. The first
VRML models were published by our group in December 1994
(Model 2) resulting from our experiments10 in what we called "molecular
collaboratories" using the newly introduced UK high speed
national computer network. These models retained the
familiar wireframe, ball and stick, spacefill or ribbon
representations of molecules, but enabled the rich
navigation features of VRML (Model 1), and the ability to
define hyperlinks from individual regions of the molecule
to other Internet resources, in much the same way as HTML
allows such hyperlinks in text-based documents.

Model 2.An
early VRML model showing the 3CRO protein/DNA
complex.

Another great advantage of
VRML is that it can be readily extended to displaying more
complex chemicals such as ionic lattices, large
biopolymers, carbohydrates, peptides, liquid crystals etc.
These often require different symbolic representations to
illustrate the key features. Some excellent examples of
this type of application emerged from Brickmann's11 group in Darmstadt from 1995
onwards. Their work shows how more complex models (Model
3)11 can reveal the 3D structure of e.g.
the p53 tumor suppressor protein complexed with a DNA helix
(blue); the peptide backbone of the protein is rendered as
a ribbon, with the computed electrostatic potentials at the
interface being projected onto the respective Van der Waals
surfaces of the molecules. The red groups are the "mutation
hotspots".

Hewat in Grenoble12 showed early on how a VRML
representation (Model 4) of the structure of the
high-temperature superconductor
Y2Ba4Cu7O15,
composed of alternating
Y1Ba2Cu3 and
Y1Ba2Cu4 units could be
constructed dynamically from a set of options and
parameters provided by the user via a Web-based form.

In principle, any computed
molecular surface can be represented in VRML. Model 5
illustrates a model showing the HOMO orbital computed for a
supermolecule corresponding to the peripheral
light-harvesting complex (LH2) of purple photosynthetic
bacteria.The structure includes two transmembrane
polypeptides and associated pigments, a pair of closely
interacting bacteriochlorophyll-a
molecules (B850) and a carotenoid (Car) unit. Constructing
such models enables detailed investigation of the method of
energy transfer via electrons and protons in photosynthetic
bacteria.

2. Knowledge Discovery and Data Mining

Bragg once said that "the
important thing in science is not so much to obtain new
facts, as to obtain new ways of thinking about them".
Knowledge discovery in databases (KDD), or,
more popularly, "data mining", has generated a great deal
of interest in recent years as vast quantities of
information have begun to accumulate in databases. The
objective is to be able to trawl these databases in novel
ways so as to discover unusual relations and correlations
between and within the data. We have applied VRML13 to the problem of representing 3D
information "mined" from e.g. the Cambridge
Crystallographic Database14 to
help identify the characteristics of weak intermolecular
hydrogen bonding interactions around aromatic systems
(Model 6). Visual representations can allow certain
attributes in the data to be noticed precisely because they
are unusual. A VRML-based model permits us to view
different types of data collected together in one scene,
and to make links between different levels in the data
hierarchy to allow probing of any unusual facets that may
emerge in a highly intuitive manner.

The model shows the results of a search for short contacts
of some typical hydrogen bond acceptor groups to a
chlorobenzene ring, normalised against the Connolly surface,
i.e. that portion of the van der Waals surface that is
accessible to a probe of finite radius. Such an approach makes
no presuppositions but rather reveals structural preferences,
as is borne out by the fact that the vast majority of the
contact vectors are oriented towards the ring hydrogens. The
conversion to VRML allows for the vectors,
colour coded according to the type of contact group, to be
hyperlinked to a second model which in turn can be used to
highlight the significant interaction, and give other
information such as the unit cell and a literature reference.
This reference in turn can be a link to the original electronic
journal article which allows the research to progress from the
discovery of a potentially interesting effect to reading the
original article about it.

Another application of data mining is illustrated in the Panel, which shows how subtle
structure-activity phenomena such as hydrogen bonding can be
teased out of large amounts of numerical data provided by the
technique of molecular modelling.15

3. Animation

Adding time-dependence to a model can often enhance the
perception and understanding of a subtle chemical
phenomenon. We experienced this directly when studying
the potential energy surface of a sequence of pericyclic
reactions starting at 1 or 2 and forming
cyclo-octatetraene (4). After a conventional
article had been prepared for printed publication,16 we decided to enhance
it for an electronic version of the journal17 by including selected
3D models, and animating those models to show normal
vibrational modes. Whilst proof-reading the "enhanced"
article, it suddenly dawned on us that the animated mode
for one geometry in particular had unexpected
characteristics.

Ostensibly, the reaction corresponded to two
synchronous electrocyclic ring openings proceeding in a
particular manner known as conrotation. Each individual
ring opening is, according to a theory first proposed by
Woodward and Hoffmann, thermally allowed. From another
perspective however, the reaction also corresponded to a
cyclo elimination reaction thermally forbidden by the
Woodward-Hoffmann rules. How could both interpretations
be true? Focusing our eyes on the four atoms
corresponding to the cyclo elimination, we realised by
watching the animation that the Woodward-Hoffmann
forbidden characteristics were in fact avoided by a
pronounced lateral dislocation of the two reacting
centres (Model 7). If you are reading this article in
print, and are having difficulty visualising what we mean
by that, we strongly urge you to view the animated VRML
model to see how we obtained our original insight.18

Model 7.An animated model showing vibrational modes.

Simple animations of this type can also be accomplished
using other tools for displaying molecular models such as Chime
for molecules or spectra19, but this requires a set of
molecular coordinates for every frame of the animation. VRML
often requires only the starting and ending coordinates of the
molecule. The properties of the various objects within a VRML
scene are then interpolated at each time step to create the
effect of an animation. Such a technique is particularly
effective when animations of large molecules are required.

4. Virtual Laboratories

A quite different application of VRML illustrates how laboratory instrumentation or
apparatus might be depicted (Model 8).20 Having a more "lifelike"
rendition may make it easier for others to reconstruct a
complex experimental set-up. It is also possible to make
the model interactive to facilitate the appraisal of
modifications to the scheme. For example, various VRML
laboratory components or "objects" could be connected
together with the help of a VRML authoring tool from an
on-line "storeroom". The virtual approach would also
provide a means for students to gain some insight to
modern laboratory techniques that might otherwise be
prohibitively expensive to actually carry out.
Ultimately, a network of virtual instruments
corresponding to the layout of real world laboratory
environment could be constructed, and virtual experiments
within the laboratories could correspond to live
experiments.

In the scene shown here, each important object is
assigned a "viewpoint" to help in the navigation, and
these viewpoints could be used to index the model, and
ultimately to search for model components on a global
scale.

There is even the possibility that a real instrument could
be depicted and even controlled remotely, in a manner analogous
to the automated process controls in a chemical plant. An
automated laboratory driven largely by robotics could be
managed by an expert from practically anywhere in the world.
The clear advantage here is that several such laboratories can
be managed by the same person. If the VRML world reflects real
world applications, many challenging issues arise. In the case
of the virtual laboratory, a mechanism is required whereby the
laboratory information is transferred to the VRML scene. If the
laboratory information is stored in databases this would entail
suitable integration between the VRML model and the database.
This can be achieved using a technique known as VRML scripting.
Here, little programs are embedded within the VRML model giving
it behaviour characteristics. For example, one such program
might give a simple VRML model of a clamp the ability to pivot,
or in a molecular model, a program might be embedded to
calculate a required property of the molecule.

Concluding Remarks

In describing their subject in print, chemists have hitherto
had to rely on static two dimensional visual devices such as
figures, diagrams and schemes. The introduction of tools such
VRML and the World-Wide Web has added the dynamic "model" to
this repertoire18. We anticipate
that VRML or similar tools for constructing complex visual
models will gradually become incorporated into mainstream
electronic journals17, books and
other electronic publications. As the chemical content carried
by such models becomes richer, a major challenge for the future
will be the development of effective means of indexing these
models in a chemically meaningful manner, and creating a
mechanism to search for specified components of such models on
a global scale.

Full details of the history and
specifications can be seen at the VRML repository at http://www.sdsc.edu/vrml/.
This site also contains a comprehensive list of available
software and examples of VRML models.